Therapeutic ultrasound attenuates DSS-induced colitis through the cholinergic anti-inflammatory pathway
| Autor: | Fabiany da Costa Gonçalves, Fernanda Visioli, Natalia S. Nunes, Scott R. Burks, Joseph A. Frank, Parwathy Chandran, Maggie Sundby, Ana Helena da Rosa Paz |
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| Rok vydání: | 2019 |
| Předmět: |
Acute ulcerative colitis
α7 nicotinic acetylcholine receptor Proteomics 0301 basic medicine medicine.medical_specialty Research paper alpha7 Nicotinic Acetylcholine Receptor Ultrasonic Therapy Therapeutic ultrasound Gastroenterology Inflammatory bowel disease General Biochemistry Genetics and Molecular Biology Mice 03 medical and health sciences 0302 clinical medicine Immune system Cholinergic anti-inflammatory pathway Internal medicine medicine Animals Humans Colitis Acute colitis Peroxidase Inflammation Mice Knockout Dextran Sulphate sodium business.industry Macrophages Dextran Sulfate Acute kidney injury General Medicine Inflammatory Bowel Diseases medicine.disease Ulcerative colitis 3. Good health Disease Models Animal 030104 developmental biology 030220 oncology & carcinogenesis Cytokines Cholinergic business |
| Zdroj: | EBioMedicine |
| ISSN: | 2352-3964 |
| DOI: | 10.1016/j.ebiom.2019.06.033 |
| Popis: | Background Ulcerative Colitis (UC) is an Inflammatory Bowel Disease (IBD) characterized by uncontrolled immune response, diarrhoea, weight loss and bloody stools, where sustained remission is not currently achievable. Dextran Sulphate Sodium (DSS)-induced colitis is an animal model that closely mimics human UC. Ultrasound (US) has been shown to prevent experimental acute kidney injury through vagus nerve (VN) stimulation and activation of the cholinergic anti-inflammatory pathway (CAIP). Since IBD patients may present dysfunctional VN activity, our aim was to determine the effects of therapeutic ultrasound (TUS) in DSS-induced colitis. Methods Acute colitis was induced by 2% DSS in drinking water for 7 days and TUS was administered to the abdominal area for 7 min/day from days 4–10. Clinical symptoms were analysed, and biological samples were collected for proteomics, macroscopic and microscopic analysis, flow cytometry and immunohistochemistry. Findings TUS attenuated colitis by reducing clinical scores, colon shortening and histological damage, inducing proteomic tolerogenic response in the gut during the injury phase and early recovery of experimental colitis. TUS did not improve clinical and pathological outcomes in splenectomised mice, while α7nAChR (α7 nicotinic acetylcholine receptor - indicator of CAIP involvement) knockout animals presented with disease worsening. Increased levels of colonic F4/80+α7nAChR+ macrophages in wild type mice suggest CAIP activation. Interpretation These results indicate TUS improved DSS-induced colitis through stimulation of the splenic nerve along with possible contribution by VN with CAIP activation. Fund Intramural Research Programs of the Clinical Centre, the National Institute of Biomedical Imaging and Bioengineering at the NIH and CAPES/Brazil. Graphical abstract Unlabelled Image |
| Databáze: | OpenAIRE |
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